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2015 ; 10
(6
): 1021-30
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gab.com Text
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English Wikipedia
Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during
the Treatment of Secondary Hyperparathyroidism
#MMPMID25873267
Sprague SM
; Wetmore JB
; Gurevich K
; Da Roza G
; Buerkert J
; Reiner M
; Goodman W
; Cooper K
Clin J Am Soc Nephrol
2015[Jun]; 10
(6
): 1021-30
PMID25873267
show ga
BACKGROUND AND OBJECTIVES: Cinacalcet and vitamin D are often combined to treat
secondary hyperparathyroidism (SHPT) in patients on dialysis. Independent effects
on fibroblast growth factor-23 (FGF-23) concentrations in patients on
hemodialysis administered cinacalcet or vitamin D analogs as monotherapies during
treatment of SHPT are evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A
multicenter, randomized, open-label study to compare the efficacy of cinacalcet
versus traditional vitamin D therapy for management of secondary
hyperparathyroidism among subjects undergoing hemodialysis (PARADIGM) was a
prospective, phase 4, multicenter, randomized, open-label study conducted
globally. Participants (n=312) were randomized 1:1 to cinacalcet (n=155) or
vitamin D analog (n=157) for 52 weeks. Levels of FGF-23 were measured at baseline
and weeks 20 and 52. The absolute and percentage changes from baseline in plasma
FGF-23, parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and
calcium-phosphorus product (Ca×P) were assessed. Correlations and logistic
regression were used to explore relationships between changes in FGF-23 and
changes in PTH, Ca, P, and Ca×P from baseline to week 52 by treatment arm.
RESULTS: Median (quartiles 1, 3) decrease in FGF-23 concentrations was observed
in the cinacalcet arm (-40%; -63%, 16%) compared with median increase in the
vitamin D analog arm (47%; 0%, 132%) at week 52 (P<0.001). Changes in FGF-23 in
both arms were unrelated to changes in PTH (cinacalcet: r=0.17, P=0.11; vitamin D
analog: r=-0.04, P=0.70). Changes in FGF-23 in the vitamin D analog but not the
cinacalcet arm were correlated with changes in Ca (cinacalcet: r=0.11, P=0.30;
vitamin D analog: r=0.32, P<0.01) and P (cinacalcet: r=0.19, P=0.07; vitamin D
analog: r=0.49, P<0.001). Changes in FGF-23 were correlated with changes in Ca×P
in both arms (cinacalcet: r=0.26, P=0.01; vitamin D analog: r=0.57, P<0.001).
Independent of treatment arm, participants with reductions in P or Ca×P were
significantly more likely to show reductions in FGF-23. CONCLUSIONS: During
treatment of SHPT, cinacalcet use was associated with a decrease in FGF-23
concentrations, whereas vitamin D analogs were associated with an increase. The
divergent effects of these treatments on FGF-23 seem to be independent of
modification of PTH. It is possible that effects of cinacalcet and vitamin D
analogs on FGF-23 may be mediated indirectly by other effects on bone and mineral
metabolism.
|*Renal Dialysis/adverse effects
[MESH]
|Aged
[MESH]
|Australia
[MESH]
|Biomarkers/blood
[MESH]
|Calcimimetic Agents/adverse effects/*therapeutic use
[MESH]
|Calcium/blood
[MESH]
|Canada
[MESH]
|Chi-Square Distribution
[MESH]
|Cinacalcet/adverse effects/*therapeutic use
[MESH]